Evidence is mounting that visceral mechanisms play an important role in hunger, thirst and satiety. Our previous work and that of others suggest that the liver and duodenum contain receptors innervated by the vagus and the sympathetic nervous system which inform the brain of the nutritional state of the organism. We plan to look for the role of peripheral glucoreceptors as well as receptors for other nutrients in this control. Using anti-metabolites of glucose we want to see the role of the autonomic innervation of the liver in controlling food intake. Also of interest is the possible presence of osmoreceptors in the liver that may be involved in controlling water intake. We want to look at feeding patterns in animals deprived of viseral input. Certain hormones and chemicals transmitters of particular interest are glucagon and 5- hydroxytryptamine. We plan to use alpha cytotoxic agents to cause a permanent decrease in glucagon availability to see if this affects satiety mechanisms in any way. We have also proposed a mechanism whereby peripheral stores of 5HT might interact with vagally mediated satiety mechanisms to control food intake. This will be investigated by behavioral measures of hunger following 5HT infusions under a variety of conditions as well as microelectrode recording of neurons in the vagal relay nucleus and the hypothalamus following 5HT and nutrient infusions in hepatic-portal vein and duodenum respectively.